Analytical sample preparation strategies for the determination of antimalarial drugs in human whole blood, plasma and urine

• Antimalarials have been determined in whole blood, plasma and urine.
• Dried blood spot, protein precipitation and dilution are combined with liquid–liquid extraction, and solid-phase extraction.
• The DBS method is safer than whole blood and good for field studies but can cause severe analyte losses.
• Protein precipitation is good for lipophilic compounds but may cause degradation of artemisinin-based drugs.
• SPE is frequently used for extraction of artemisinin and its derivates because it minimizes contact with organic solvents.

Antimalarial drugs commonly referred to as antimalarials, include a variety of compounds with different physicochemical properties. There is a lack of information on antimalarial distribution in the body over time after administration, e.g. the drug concentrations in whole blood, plasma, and urine, which must be improved in order to advance curing the parasitic disease malaria. A key problem also lies in that pharmacokinetic studies not always are performed in patient groups that may benefit most of the treatment such as children, pregnancy and lower-weight ethnic populations. Here we review the available sample preparation strategies combined with liquid chromatographic (LC) analysis to determine antimalarials in whole blood, plasma and urine published over the last decade. Sample preparation can be done by protein precipitation, solid-phase extraction, liquid–liquid extraction or dilution. After LC separation, the preferred detection tool is tandem mass spectrometry (MS/MS) but other detection methods have been used e.g. UV, fluorescence and electrochemical detection. Major trends for sample preparation of the different groups of antimalarials for each matrix and its detection have been summarized. Finally, the main problems that the researchers have dealt with are highlighted. This information will aid analytical chemists in the development of novel methods for determining existing antimalarials and upcoming new drugs.